Randomised Clinical Trial to Evaluate the Efficacy of Acetazolamide for the Treatment of Cystoid Fluid Collections in X-Linked Retinoschisis: The AXIS Trial.

BACKGROUND: This trial aimed to evaluate the efficacy of oral acetazolamide in reducing cystoid fluid collections (CFC) and improving visual function in patients with X-linked retinoschisis (XLRS). METHODS: In this investigator-initiated, single centre, open-label, randomised controlled trial, XLRS patients aged ≥ 12 years with fovea-involving CFC at baseline were eligible. Participants were randomised 1:1 to receive either oral acetazolamide (500 mg/day for 16 weeks, followed by tapering or discontinuation based on response) or no treatment (control) for 32 weeks. Seven study visits were completed over 32 weeks. The primary outcome was central subfield thickness (CST). Secondary outcomes included functional and structural measures, as well as patient-reported visual disability. RESULTS: A total of 19 patients were enrolled: 10 received acetazolamide (17 eyes), and nine were monitored without treatment (16 eyes). The difference in CST from baseline up to week 32 between the treatment and control groups was on average +2.7 μm (p = 0.9; 95% CI, -68.1 to 73.5 μm). Retinal sensitivity on microperimetry showed a modest statistically significant improvement favouring acetazolamide. However, no significant improvements were observed for best-corrected visual acuity, low-luminance visual acuity, cystoid fluid collection volume or patient-reported visual disability in the treatment group compared to the control group. CONCLUSION: This study found no clinically meaningful benefit of oral acetazolamide for reducing CFC or improving visual function in the overall XLRS population. Although structural and functional outcomes were comparable between groups overall, a small subset of patients may experience benefit, suggesting a personalised treatment approach may be warranted.